近日，德国科隆大学教授Tatiana Korotkova小组研制了侧下丘脑神经元群表达瘦素受体抵消焦虑从而适应性行为反应。该研究于2025年10月20日发表于国际一流学术期刊《自然—神经科学》杂志上。

利用单细胞钙成像和细胞类型特异性活性操作，课题组在行为小鼠中鉴定了下丘脑外侧（LH; LepRLH）中编码焦虑刺激的瘦素敏感神经元亚群。在高度焦虑的动物中，LepRLH神经元在焦虑性刺激中分化较差，并被来自前额皮质的输入抑制。LepRLH神经元的活性预测了个体动物的焦虑水平，并且LepRLH神经元的激活使焦虑条件下的适应性反应-在厌食症神经疾病模型中探索新地形，在焦虑环境中进食和限制不适应的过度运动。因此，LH中瘦素敏感的神经元亚群能够在健康和病理状态下，在焦虑条件下适应性地满足重要需求。

据介绍，促进适应策略的神经元机制，使动物在威胁的情况下克服焦虑仍然未知。

附：英文原文

Title: A lateral hypothalamic neuronal population expressing leptin receptors counteracts anxiety to enable adaptive behavioral responses

Author: Figge-Schlensok, Rebecca, Petzold, Anne, Hugger, Nele, Bakhareva, Alisa, Abdallah, Ali Taleb, Wissing, Chantal, van den Munkhof, Hanna Elin, Witt, Marla Yasmin, Awad, Deema Imad, Korotkova, Tatiana

Issue&Volume: 2025-10-20

Abstract: Neuronal mechanisms that facilitate adaptive strategies to enable an animal to overcome anxiety in threatening situations remain unknown. Using single-cell calcium imaging and cell-type-specific activity manipulations in behaving mice, we identified leptin-sensitive neuronal subpopulations in the lateral hypothalamus (LH; LepRLH) that encode anxiogenic stimuli. In high-anxiety animals, LepRLH neurons differentiated poorly among anxiogenic stimuli and were inhibited by input from the prefrontal cortex. The activity of LepRLH neurons predicted the anxiety level of individual animals, and the activation of LepRLH neurons enabled adaptive responses under anxiogenic conditions—exploration of new terrain, eating despite anxiogenic environment and limiting maladaptive excessive locomotion in an anorexia nervosa disease model. Thus, leptin-sensitive neuronal subpopulations in the LH enable adaptive fulfillment of vital needs despite anxiogenic conditions, both in healthy and pathological states.

DOI: 10.1038/s41593-025-02078-y

Source: https://www.nature.com/articles/s41593-025-02078-y